The loss of upper airway muscle tone in sleep is the precipitating cause of sleep apnea. Sleep apnea affects 3-5% of men over 40 and 1.5-2.5% of post-menopausal women. It causes persistent sleepiness, exacerbates a variety of medical conditions and increases morbidity and mortality. We will study how forebrain sleep induction mechanisms cause the reduction of muscle tone in airway dilators. A variety of complementary techniques will be used in sleep apnea patients to determine which forebrain and brainstem regions are activated and inactivated during airway obstruction. In projects 2 and 3 the pathways from forebrain sleep inducing regions will be traced to the brainstem region activated and inactivated in sleep apnea, focusing on regions controlling upper airway muscle tone. These studies will use anatomical tract tracing techniques, thermal activation of sleep controlling neurons and unit recording in the posterior hypothalamus, periaqueductal gray and medulla of unrestrained animals. In projects 4 and 5 we will determine which amino acid and monoamine transmitters mediate the suppression of muscle tone in airway dilator motoneurons during REM and non-REM sleep. These studies will use in vivo microdialysis, intracellular unit recording and iontophoresis. This program will bring basic science techniques to bear on the important clinical problem of sleep apnea. Pilot studies for this collaborative enterprise have already yield data that will produce a major revision in our understanding of the mechanisms controlling the airway during sleep. The work of this SCOR (Specialized Center of Research) will increase our understanding of sleep apnea. It is also likely to be of importance to other disorders of motor control during sleep. It is also likely to be of importance to other disorders of motor control during sleep, including REM sleep behavior disorder, bruxism, periodic limb movements during sleep and cataplexy. This research will also shed light on the cellular mechanisms controlling REM and non-REM sleep states.